| Title | Gender-Dependent Impairment of Cardiac Action Potential Conduction in Type 1 Diabetic Rats. | | Author(s) | Shimoni Y, Emmett T, Schmidt R, Nygren A, Kargacin GJ | | Institution | University of Calgary, Faculty of Medicine. | | Source | Am J Physiol Heart Circ Physiol 2009 Mar 13. | | Abstract | The incidence of diabetes mellitus is increasing. Cardiac dysfunction often develops, resulting in diverse arrhythmias. These arise from ion channel remodeling, or from altered speed and pattern of impulse propagation. Few studies have investigated impulse propagation in the diabetic heart. We previously showed a reduced conduction reserve in the diabetic heart, with associated changes in intercellular gap junctions. The present study investigated whether these effects are gender-specific. Hearts from control and streptozotocin-diabetic male and female rats were used. Optical mapping was performed with the voltage-sensitive dye di-4-ANEPPS, using Langendorff-perfused hearts. Isolated cells were used for immunofluorescent labeling of the gap junction protein connexin 43. The gap junction uncoupler heptanol (0.75 mM), or elevated K(+) (9 mM, to reduce cell excitability) produced significantly greater slowing of propagation in diabetic males than females. In ovariectomized diabetic females, 9 mM K(+) slowed conduction significantly more than in non-ovariectomized females. The subcellular redistribution (lateralization) of the gap junction protein connexin (Cx) 43 was smaller in diabetic females. Pre-treatment of diabetic males with the ACE inhibitor quinapril reduced Cx43 lateralization and the effects of 9 mM K(+) on propagation. In conclusion, the slowing of cardiac impulse propagation in type 1 diabetes is smaller in female rats, partly due to the presence of female sex hormones. This difference is (partly) mediated by gender differences in activation of the cardiac renin-angiotensin system. Key words: Diabetes, gender, impulse propagation, gap junction. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19286947 |
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